tbuckley/cabot-search huggingface dataset:
Chromothripsis is a frequent event and underlies typical genetic changes in early T-cell precursor lymphoblastic leukemia in adults
Authors: Silvia Arniani, Valentina Pierini, Fabrizia Pellanera, Caterina Matteucci, Danika Di Giacomo, Valentina Bardelli, Martina Quintini, Elena Mavridou, Anair Graciela Lema Fernandez, Carlotta Nardelli, Martina Moretti, Paolo Gorello, Barbara Crescenzi, Silvia Romoli, Donatella Beacci, Marco Cerrano, Nicola Fracchiolla, Simona Sica, Fabio Forghieri, Fabio Giglio, Michela Dargenio, Loredana Elia, Roberta La Starza, Cristina Mecucci
Journal: Leukemia (2022)

Chromothripsis is a mitotic catastrophe that arises from multiple double strand breaks and incorrect re-joining of one or a few chromosomes. We report on incidence, distribution, and features of chromothriptic events in T-cell acute lymphoblastic leukemias (T-ALL). SNP array was performed in 103 T-ALL (39 ETP/near ETP, 59 non-ETP, and 5 with unknown stage of differentiation), including 38 children and 65 adults. Chromothripsis was detected in 11.6% of all T-ALL and occurred only in adult cases with an immature phenotype (12/39 cases; 30%). It affected 1 to 4 chromosomes, and recurrently involved chromosomes 1, 6, 7, and 17. Abnormalities of genes typically associated with T-ALL were found at breakpoints of chromothripsis. In addition, it gave rise to new/rare alterations, such as, the SFPQ::ZFP36L2 fusion, reported in pediatric T-ALL, deletions of putative suppressors, such as IKZF2 and CSMD1, and amplification of the BCL2 gene. Compared to negative cases, chromothripsis positive T-ALL had a significantly higher level of MYCN expression, and a significant downregulation of RGCC, which is typically induced by TP53 in response to DNA damage. Furthermore we identified mutations and/or deletions of DNA repair/genome stability genes in all cases, and an association with NUP214 rearrangements in 33% of cases.
Pancreatic PCSK9 controls the organization of the β-cell secretory pathway via LDLR-cholesterol axis
Authors: Algerta Marku, Lorenzo Da Dalt, Alessandra Galli, Nevia Dule, Paola Corsetto, Angela Maria Rizzo, Annalisa Moregola, Patrizia Uboldi, Fabrizia Bonacina, Paola Marciani, Michela Castagna, Alberico Luigi Catapano, Giuseppe Danilo Norata, Carla Perego
Journal: Metabolism (2022)
Modified risk-stratified sequential treatment (subcutaneous rituximab with or without chemotherapy) in B-cell Post-transplant lymphoproliferative disorder (PTLD) after Solid organ transplantation (SOT): the prospective multicentre phase II PTLD-2 trial
Authors: Heiner Zimmermann, Christian Koenecke, Martin H. Dreyling, Christiane Pott, Ulrich Dührsen, Dennis Hahn, Norbert Meidenbauer, Ingeborg A. Hauser, Mathias J. Rummel, Dominik Wolf, Michael Heuser, Christian Schmidt, Peter Schlattmann, Matthias Ritgen, Reiner Siebert, Ilske Oschlies, Ioannis Anagnostopoulos, Ralf U. Trappe
Journal: Leukemia (2022)

The prospective multicentre Phase II PTLD-2 trial (NCT02042391) tested modified risk-stratification in adult SOT recipients with CD20-positive PTLD based on principles established in the PTLD-1 trials: sequential treatment and risk-stratification. After rituximab monotherapy induction, patients in complete remission as well as those in partial remission with IPI < 3 at diagnosis (low-risk) continued with rituximab monotherapy and thus chemotherapy free. Most others (high-risk) received R-CHOP-21. Thoracic SOT recipients who progressed (very-high-risk) received alternating R-CHOP-21 and modified R-DHAOx. The primary endpoint was event-free survival (EFS) in the low-risk group. The PTLD-1 trials provided historical controls. Rituximab was applied subcutaneously. Of 60 patients enrolled, 21 were low-risk, 28 high-risk and 9 very-high-risk. Overall response was 45/48 (94%, 95% CI 83-98). 2-year Kaplan-Meier estimates of time to progression and overall survival were 78% (95% CI 65-90) and 68% (95% CI 55-80) - similar to the PTLD-1 trials. Treatment-related mortality was 4/59 (7%, 95% CI 2-17). In the low-risk group, 2-year EFS was 66% (95% CI 45-86) versus 52% in the historical comparator that received CHOP (p = 0.432). 2-year OS in the low-risk group was 100%. Results with R-CHOP-21 in high-risk patients confirmed previous results. Immunochemotherapy intensification in very-high-risk patients was disappointing.
Activation of the Tubulo-Glomerular Feedback by SGLT2 Inhibitors in Patients With Type 2 Diabetes and Advanced Chronic Kidney Disease: Toward the End of a Myth?
Authors: Alexandre O. Gérard, Audrey Laurain, Guillaume Favre, Milou-Daniel Drici, Vincent L.M. Esnault
Journal: Diabetes Care (2022)
Three-dimensional Augmented Reality–guided Robotic-assisted Kidney Transplantation: Breaking the Limit of Atheromatic Plaques
Authors: Alberto Piana, Andrea Gallioli, Daniele Amparore, Pietro Diana, Angelo Territo, Riccardo Campi, Josep Maria Gaya, Lluis Guirado, Enrico Checcucci, Andrea Bellin, Joan Palou, Sergio Serni, Francesco Porpiglia, Alberto Breda
Journal: European Urology (2022)
A novel decellularized matrix of Wnt signaling-activated osteocytes accelerates the repair of critical-sized parietal bone defects with osteoclastogenesis, angiogenesis, and neurogenesis
Authors: Xiaofang Wang, Yufei Ma, Jie Chen, Yujiao Liu, Guangliang Liu, Pengtao Wang, Bo Wang, Makoto M. Taketo, Teresita Bellido, Xiaolin Tu
Journal: Bioactive Materials (2022)

Cell source is the key to decellularized matrix (DM) strategy. This study compared 3 cell types, osteocytes with/without dominant active Wnt/β-catenin signaling (daCO and WTO) and bone marrow stromal cells (BMSCs) for their DMs in bone repair. Decellularization removes all organelles and >95% DNA, and retained >74% collagen and >71% GAG, maintains the integrity of cell basement membrane with dense boundaries showing oval and honeycomb structure in osteocytic DM and smooth but irregular shape in the BMSC-DM. DM produced higher cell survival rate (90%) and higher proliferative activity. In vitro, daCO-DM induces more and longer stress fibers in BMSCs, conducive to cell adhesion, spreading, and osteogenic differentiation. 8-wk after implantation of the critical-sized parietal bone defect model, daCO-DM formed tight structures, composed of a large number of densely-arranged type-I collagen under polarized light microscope, which is similar to and integrated with host bone. BV/TV (>54%) was 1.5, 2.9, and 3.5 times of WTO-DM, BMSC-DM, and none-DM groups, and N.Ob/T.Ar (3.2 × 102/mm2) was 1.7, 2.9, and 3.3 times. At 4-wk, daCO-DM induced osteoclastogenesis, 2.3 times higher than WTO-DM; but BMSC-DM or none-DM didn't. daCO-DM increased the expression of RANKL and MCSF, Vegfa and Angpt1, and Ngf in BMSCs, which contributes to osteoclastogenesis, angiogenesis, and neurogenesis, respectively. daCO-DM promoted H-type vessel formation and nerve markers β3-tubulin and NeuN expression. Conclusion: daCO-DM produces metabolic and neurovascularized organoid bone to accelerate the repair of bone defects. These features are expected to achieve the effect of autologous bone transplantation, suitable for transformation application.
Immune Checkpoint Inhibitor-Related Pneumonia in Unresectable Hepatocellular Carcinoma: Two Fatal Cases under Atezolizumab plus Bevacizumab
Authors: Kei Endo, Hidekatsu Kuroda, Takayoshi Oikawa, Yuma Ito, Tamami Abe, Youhei Kooka, Keisuke Kakisaka, Akio Miyasaka, Tamotsu Sugai, Takayuki Matsumoto
Journal: Liver Cancer (2022)

No abstract due to Letter.
Delphi Panel Consensus Recommendations for Screening and Managing Childhood Cancer Survivors at Risk for Cardiomyopathy
Authors: Rahela Aziz-Bose, Renee Margossian, Bethany L. Ames, Kerry Moss, Matthew J. Ehrhardt, Saro H. Armenian, Torunn I. Yock, Larissa Nekhlyudov, David Williams, Melissa Hudson, Anju Nohria, Lisa B. Kenney
Journal: JACC CardioOncology (2022)

Cardiomyopathy is a leading cause of late morbidity and mortality in childhood cancer survivors (CCS). Evidence-based guidelines recommend risk-stratified screening for cardiomyopathy, but the management approach for abnormalities detected when screening asymptomatic young adult CCS is poorly defined.The aims of this study were to build upon existing guidelines by describing the expert consensus-based cardiomyopathy screening practices, management approach, and clinical rationale for the management of young adult CCS with screening-detected abnormalities and to identify areas of controversy in practice.A multispecialty Delphi panel of 40 physicians with expertise in cancer survivorship completed 3 iterative rounds of semi-open-ended questionnaires regarding their approaches to the management of asymptomatic young adult CCS at risk for cardiomyopathy (screening practices, referrals, cardiac testing, laboratory studies, medications). Consensus was defined as ≥90% panelist agreement with recommendation.The response rate was 100% for all 3 rounds. Panelists reached consensus on the timing and frequency of echocardiographic screening for anthracycline-associated cardiomyopathy, monitoring during pregnancy, laboratory testing for modifiable cardiac risk factors, and referral to cardiology for ejection fraction ≤50% or preserved ejection fraction with diastolic dysfunction. Controversial areas (<75% agreement) included chest radiation dose threshold to merit screening, indications for advanced cardiac imaging and cardiac serum biomarkers for follow-up of abnormal echocardiographic findings, and medical management of asymptomatic left ventricular systolic dysfunction.Expert practice is largely consistent with existing risk-based screening guidelines. Some recommendations for managing abnormalities detected on screening echocardiography remain controversial. The rationale offered by experts for divergent approaches may help guide clinical decisions in the absence of guidelines specific to young adult CCS.
Linking the European Organisation for Research and Treatment of Cancer Item Library to the Common Terminology Criteria for Adverse Events
Authors: Alexandra Gilbert, Claire Piccinin, Galina Velikova, Mogens Groenvold, Dagmara Kuliś, Jane M. Blazeby, Andrew Bottomley
Journal: Journal of Clinical Oncology (2022)

The European Organisation for Research and Treatment of Cancer (EORTC) Item Library is an interactive online platform currently composed of 950 unique items (questions) derived from 67 patient-reported outcome (PRO) questionnaires. PROs complement clinician adverse event (AE) reporting classifications like the Common Terminology Criteria for Adverse Events (CTCAE). This work aims to create a standardized framework using the CTCAE to systematically classify symptomatic AEs from the EORTC Item Library through linking individual items to corresponding AEs.
Heart Disease and Stroke Statistics—2013 Update
Authors: Alan S. Go, Dariush Mozaffarian, Véronique L. Roger, Emelia J. Benjamin, Jarett D. Berry, William B. Borden, Dawn M. Bravata, Shifan Dai, Earl S. Ford, Caroline S. Fox, Sheila Franco, Heather J. Fullerton, Cathleen Gillespie, Susan M. Hailpern, John A. Heit, Virginia J. Howard, Mark D. Huffman, Brett M. Kissela, Steven J. Kittner, Daniel T. Lackland, Judith H. Lichtman, Lynda D. Lisabeth, David Magid, Gregory M. Marcus, Ariane Marelli, David B. Matchar, Darren K. McGuire, Emile R. Mohler, Claudia S. Moy, Michael E. Mussolino, Graham Nichol, Nina P. Paynter, Pamela J. Schreiner, Paul D. Sorlie, Joel Stein, Tanya N. Turan, Salim S. Virani, Nathan D. Wong, Daniel Woo, Melanie B. Turner
Journal: Circulation (2012)
SARS-CoV-2 breakthrough infection in vaccinees induces virus-specific nasal-resident CD8+ and CD4+ T cells of broad specificity
Authors: Joey Ming Er Lim, Anthony Tanoto Tan, Nina Le Bert, Shou Kit Hang, Jenny Guek Hong Low, Antonio Bertoletti
Journal: The Journal of Experimental Medicine (2022)

Rapid recognition of SARS-CoV-2-infected cells by resident T cells in the upper airway might provide an important layer of protection against COVID-19. Whether parenteral SARS-CoV-2 vaccination or infection induces nasal-resident T cells specific for distinct SARS-CoV-2 proteins is unknown. We isolated T cells from the nasal mucosa of COVID-19 vaccinees who either experienced SARS-CoV-2 infection after vaccination (n = 34) or not (n = 16) and analyzed their phenotype, SARS-CoV-2 specificity, function, and persistence. Nasal-resident SARS-CoV-2-specific CD8+ and CD4+ T cells were detected almost exclusively in vaccinees who experienced SARS-CoV-2 breakthrough infection. Importantly, the Spike-specific T cells primed by vaccination did not suppress the induction of T cells specific for other SARS-CoV-2 proteins. The nasal-resident T cell responses persisted for ≥140 d, with minimal sign of waning. These data highlight the importance of viral nasal challenge in the formation of SARS-CoV-2-specific antiviral immunity at the site of primary infection and further define the immunological features of SARS-CoV-2 hybrid immunity.
Perfecting antigen prediction
Authors: David Hoyos, Benjamin D. Greenbaum
Journal: The Journal of Experimental Medicine (2022)

Advances in genomics and precision measurement have continued to demonstrate the importance of the immune system across many disease types. At the heart of many emerging approaches to leverage these insights for precision immunotherapies is the computational antigen prediction problem. We propose a threefold approach to improving antigen predictions: further defining the geometry of the antigen landscape, incorporating the coupling of antigen recognition to other cellular processes, and diversifying the training sets used for models that predict immunogenicity.
Attenuation of Proteasome-Induced Proteolysis in Skeletal Muscle by β-Hydroxy-β-Methylbutyrate in Cancer-Induced Muscle Loss
Authors: Helen J. Smith, Pradip Mukerji, Michael J. Tisdale
Journal: Cancer Research (2005)

Abstract Loss of skeletal muscle is an important determinant of survival in patients with cancer-induced weight loss. The effect of the leucine metabolite β-hydroxy-β-methylbutyrate (HMB) on the reduction of body weight loss and protein degradation in the MAC16 model of cancer-induced weight loss has been compared with that of eicosapentaenoic acid (EPA), a recognized inhibitor of protein degradation. HMB was found to attenuate the development of weight loss at a dose greater than 0.125 g/kg accompanied by a small reduction in tumor growth rate. When EPA was used at a suboptimal dose level (0.6 g/kg) the combination with HMB seemed to enhance the anticachectic effect. Both treatments caused an increase in the wet weight of soleus muscle and a reduction in protein degradation, although there did not seem to be a synergistic effect of the combination. Proteasome activity, determined by the “chymotrypsin-like” enzyme activity, was attenuated by both HMB and EPA. Protein expression of the 20S α or β subunits was reduced by at least 50%, as were the ATPase subunits MSS1 and p42 of the 19S proteasome regulatory subunit. This was accompanied by a reduction in the expression of E214k ubiquitin-conjugating enzyme. The combination of EPA and HMB was at least as effective or more effective than either treatment alone. Attenuation of proteasome expression was reflected as a reduction in protein degradation in gastrocnemius muscle of cachectic mice treated with HMB. In addition, HMB produced a significant stimulation of protein synthesis in skeletal muscle. These results suggest that HMB preserves lean body mass and attenuates protein degradation through down-regulation of the increased expression of key regulatory components of the ubiquitin-proteasome proteolytic pathway, together with stimulation of protein synthesis.
Linking Clinical Variables With Health-Related Quality of Life
Authors: Ira B. Wilson
Journal: JAMA (1995)

HEALTH-related quality of life (HRQL) is increasingly used as an outcome in clinical trials, effectiveness research, and research on quality of care. Factors that have facilitated this increased usage include the accumulating evidence that measures of HRQL are valid and "reliable,"<sup>1</sup>the publication of several large clinical trials showing that these outcome measures are responsive to important clinical changes,<sup>2-5</sup>and the successful development and testing of shorter instruments that are easier to understand and administer.<sup>6-13</sup>Because these measures describe or characterize what the patient has experienced as the result of medical care, they are useful and important supplements to traditional physiological or biological measures of health status. Given this improved ability to assess patients' health status, how can physicians and health care systems intervene to improve HRQL? Implicit in the use of measures of HRQL in clinical trials and in effectiveness research is the concept that clinical
Factors Associated With Declining Lung Cancer Screening After Discussion With a Clinician in a Cohort of US Veterans
Authors: Eduardo R. Núñez, Tanner J. Caverly, Sanqian Zhang, Mark E. Glickman, Shirley X. Qian, Jacqueline H. Boudreau, Donald R. Miller, Christopher G. Slatore, Renda Soylemez Wiener
Journal: JAMA Network Open (2022)

Lung cancer screening (LCS) is underused in the US, particularly in underserved populations, and little is known about factors associated with declining LCS. Guidelines call for shared decision-making when LCS is offered to ensure informed, patient-centered decisions.
Regulation of flagellar motility and biosynthesis in enterohemorrhagic <i>Escherichia coli</i> O157:H7
Authors: Hongmin Sun, Min Wang, Yutao Liu, Pan Wu, Ting Yao, Wen Yang, Qian Yang, Jun Yan, Bin Yang
Journal: Gut Microbes (2022)

ABSTARCTEnterohemorrhagic Escherichia coli (EHEC) O157:H7 is a human pathogen that causes a variety of diseases, such as hemorrhagic colitis and lethal hemolytic uremic syndrome. Flagellum-dependent motility plays diverse roles in the pathogenesis of EHEC O157:H7, including its migration to an optimal host site, adherence and colonization, survival at the infection site, and post-infection dispersal. However, it is very expensive for cellular economy in terms of the number of genes and the energy required for flagellar biosynthesis and functioning. Furthermore, the flagellar filament bears strong antigenic properties that induce a strong host immune response. Consequently, the flagellar gene expression and biosynthesis are highly regulated to occur at the appropriate time and place by different regulatory influences. The present review focuses on the regulatory mechanisms of EHEC O157:H7 motility and flagellar biosynthesis, especially in terms of flagellar gene regulation by environmental factors, regulatory proteins, and small regulatory RNAs.
Abstract 15396: Low Levels of Adiponectin Predict the Progression of Arterial Stiffness in Patients With Hypertension
Authors: Jong-Chan Youn, Sungha Park, Donghoon Choi, Nak Hoon Son, Kwang Bok Lee, Dong-Jik Shin, Yangsoo Jang
Journal: Circulation (2010)

Background: Recent studies suggest that adiposity is associated with arterial stiffness. However, it is unclear which adipokine is related with the progression of arterial stiffness. We hypothesize...
Antibody therapy reverses biological signatures of COVID-19 progression
Authors: M. Cyrus Maher, Leah B. Soriaga, Anil Gupta, Yi-Pei Chen, Julia di Iulio, Sarah Ledoux, Megan J. Smithey, Andrea L. Cathcart, Kathleen McKusick, David Sun, Melissa Aldinger, Elizabeth Alexander, Lisa Purcell, Xiao Ding, Amanda Peppercorn, Daren Austin, Erik Mogalian, Wendy W. Yeh, Adrienne E. Shapiro, Davide Corti, Herbert W. Virgin, Phillip S. Pang, Amalio Telenti
Journal: Cell Reports Medicine (2022)

Understanding who is at risk of progression to severe coronavirus disease 2019 (COVID-19) is key to clinical decision making and effective treatment. We study correlates of disease severity in the COMET-ICE clinical trial that randomized 1:1 to placebo or to sotrovimab, a monoclonal antibody for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (ClinicalTrials.gov04545060). Laboratory parameters identify study participants at greater risk of severe disease, including a high neutrophil-to-lymphocyte ratio (NLR), a negative SARS-CoV-2 serologic test, and whole-blood transcriptome profiles. Sotrovimab treatment is associated with normalization of NLR and the transcriptomic profile and with a decrease of viral RNA in nasopharyngeal samples. Transcriptomics provides the most sensitive detection of participants who would go on to be hospitalized or die. To facilitate timely measurement, we identify a 10-gene signature with similar predictive accuracy. We identify markers of risk for disease progression and demonstrate that normalization of these parameters occurs with antibody treatment of established infection.
A single-cell transcriptional gradient in human cutaneous memory T cells restricts Th17/Tc17 identity
Authors: Christopher P. Cook, Mark Taylor, Yale Liu, Ralf Schmidt, Andrew Sedgewick, Esther Kim, Ashley Hailer, Jeffrey P. North, Paymann Harirchian, Hao Wang, Sakeen W. Kashem, Yanhong Shou, Timothy C. McCalmont, Stephen C. Benz, Jaehyuk Choi, Elizabeth Purdom, Alexander Marson, Silvia B.V. Ramos, Jeffrey B. Cheng, Raymond J. Cho
Journal: Cell Reports Medicine (2022)

The homeostatic mechanisms that fail to restrain chronic tissue inflammation in diseases, such as psoriasis vulgaris, remain incompletely understood. We profiled transcriptomes and epitopes of single psoriatic and normal skin-resident T cells, revealing a gradated transcriptional program of coordinately regulated inflammation-suppressive genes. This program, which is sharply suppressed in lesional skin, strikingly restricts Th17/Tc17 cytokine and other inflammatory mediators on the single-cell level. CRISPR-based deactivation of two core components of this inflammation-suppressive program, ZFP36L2 and ZFP36, replicates the interleukin-17A (IL-17A), granulocyte macrophage-colony-stimulating factor (GM-CSF), and interferon gamma (IFNγ) elevation in psoriatic memory T cells deficient in these transcripts, functionally validating their influence. Combinatoric expression analysis indicates the suppression of specific inflammatory mediators by individual program members. Finally, we find that therapeutic IL-23 blockade reduces Th17/Tc17 cell frequency in lesional skin but fails to normalize this inflammatory-suppressive program, suggesting how treated lesions may be primed for recurrence after withdrawal of treatment.
Apolipoprotein E4 impairs the response of neurodegenerative retinal microglia and prevents neuronal loss in glaucoma
Authors: Milica A. Margeta, Zhuoran Yin, Charlotte Madore, Kristen M. Pitts, Sophia M. Letcher, Jing Tang, Shuhong Jiang, Christian D. Gauthier, Sebastian R. Silveira, Caitlin M. Schroeder, Eleonora M. Lad, Alan D. Proia, Rudolph E. Tanzi, David M. Holtzman, Susanne Krasemann, Dong Feng Chen, Oleg Butovsky
Journal: Immunity (2022)